Method of minimizing tissue reaction during surgery with chitin

ABSTRACT

Natural or synthetic rubber surgical elements such as tubing, catheters, drains and gloves are &#34;lubricated&#34; so as to prevent sticking during storage, and permit easier emplacement, such as putting on the gloves by a surgeon or nurse, by applying to the surface of the rubber element 
     A finely divided biodegradable powder consisting essentially of 
     An enzymatically degradable form of poly(N-acetyl-D-glucosamine) selected from the group consisting of 
     Poly[N-acetyl-6-0-(carboxymethyl)-D-glucosamine], 
     Poly[N-acetyl-6-0-(2&#39;-hydroxyethyl)-D-glucosamine], 
     Poly[N-acetyl-6-0-(ethyl)-D-glucosamine], and 
     Poly(N-acetyl-D-glucosamine) itself 
     This powder is readily absorbed by living tissue without deleterious tissue reaction, thus minimizing tissue reaction from the transfer of the powder from the element such as a glove to internal sites in a subject. The gloves may be packaged in a strippable laminate package. The polymers are derived from chitin.

BACKGROUND OF THE INVENTION

This invention relates to minimizing tissue reaction in a surgicalprocedure by contacting the living tissue with a natural or syntheticrubber surgical glove which is lubricated with a finely dividedbiodegradable powder consisting essentially of an enzymaticallydegradable form of poly(N-acetyl-D-glycosamine) selected from the groupconsisting of poly[N-acetyl-6-0-(carboxymethyl)-D-glucamine],poly[N-acetyl-6-O(2'-hydroxyethyl)-D-glycosamine],poly[N-acetyl-6-0-(ethyl)-D-glusosamine], andpoly(N-acetyl-D-glucosamine) itself which form ofpoly(N-acetyl-D-glucosamine) is slowly enzymatically degraded by contactwith body tissues. Other rubber elements which contact raw tissue may besimilarly lubricated. Various dusting powders have been used on surgicalgloves for years with a prime use being to facilitate insertion of thehands of operating room personnel into natural or synthetic rubber orlatex gloves worn during surgery.

It is desirable that the powder on the gloves meet the followingrequirements:

1. It should be non-toxic to living tissue.

2. It should be biodegradable, i.e., absorbed by living tissue. This ismost important since, during surgical procedures, powder almostinevitably falls or is rubbed from the surgeon's gloved hand into anexposed body cavity, and may be carried from other areas of theoperating room into the exposed body cavity by air currents.

3. The powder should have no adverse effect within the body such as thecreation of lesions (i.e., adhesions, granulomas, or such).

4. The glove powder must be capable of sterilization by convenienthospital techniques, preferably both autoclaving and gaseous ethyleneoxide sterilization.

5. The powder must possess sufficient lubricity to permit readyinsertion of the hand into the glove and must be of sufficiently fineparticle size and have characteristics permitting such lubricity.

6. It must be reasonably priced and readily available.

7. It must be non-irriating to skin of both the surgeon or nurse and thepatient.

8. Preferably the powder resists hydrolytic degredation.

Talc was among the earliest surgical glove powders used by the medicalprofession. However, after the report by Antopol(Lycopodium Granulome,Arch. Path. 16, pg. 326(1933) that talc caused granulomas in the body,the use of talc as a glove powder was rapidly abandoned. Talc wasreplaced by starch glove powders since starch was known to bebiodegradable and was not believed to cause granulomas or otheraggravating conditions within the body. Currently, a widely usedcommercial surgical glove powder is specially treated homogeneousamylose which contains about 2 percent magnesium oxide to preventclumping of the powder.

However, starch glove powders have a number of disadvantages. They offerhigh resistance to flow and they tend to gelatinize or agglutinate inthe presence of hot water thereby creating problems when they aresterilized in a steam autoclave. Ordinarily, the starch must be treatedin some way to minimize these properties. For example, as shown in U.S.Pat. No. 2,626,257, the starch may be treated with an agent, such asepichlorohydrin, which partially etherifies the starch in order to makethe powder free flowing after steam sterilization.

Starch is also an excellent nutrient medium for virtually all vegetativebacteria such as various pathogenic microorganisms and is objectionablefor that reason.

According to Lee and Lehman(Surgery, Gynecology, and Obstetrics 84,pages 689-695(1947), starch, unlike talc, was completely absorbed withinthe peritoneal cavity without causing adhesions. This conclusion waschallenged by Sneierson and Woo(Annals of Surgery 132, pgs.1045-1050(1955) who reported two cases of large granulomas occurring insurgical wounds as a result of starch powder contamination.McAdams(Surgery 39, pgs. 329-336(1936) reported three cases ofintraperitioneal granulomas caused by starch glove powder. The Saxens(Acta Pathology Microbiology Scand. 64, pgs. 55-70 (1965) postulatedthat the magnesium oxide which acts as an anticlumping material wascausing the lesions. Myllarniemi and Frilander (Journal of theInternational College of Surgeons 44, No. 6681, pgs. 677-681 (1965)concluded that the harmful effects of starch glove powders containingmagnesium oxide might be due to a combined effect of two irritatingconstituents. Other publications which indicate the serious concern ofthe medical profession over granulomas traced to starch glove powdersare those of Lehman and Wilder (Journal of Abdominal Surgery 4, No. 3,pgs. 77-80 (1962), Webb and Regan (Archives of Surgery 84, No. 3, pgs.282-285 (1962), and Walczak and Collura (American Journal of Surgery103, No. 5, pgs. 611-612 (1962).

Despite the aforementioned disadvantages associated with starch glovepowders, they are still used by the medical profession.

U.S. Pat. No. 3,728,739 -- B. A. Semp. -- Apr. 24, 1973 STERILE SURGICALGLOVES shows rubber surgical elements such as tubing, catheters, drainsand gloves which are lubricated with finely divided polyglycolic acid.

U.S. Pat. No. 3,810,458 -- Semp. -- May 14, 1974 MINIMIZING TISSUEREACTION TO GLOVE POWDER claims a method of minimizing tissue reactionin a surgical procedure by using a rubber surgical element having alubricity imparting quantity of a finely divided biodegradable polymercontaining hydrolytically degradable glycolic acid ester linkages.

U.S. Pat. No. 3,892,314 -- Semp. -- July 1, 1975 STERILE RUBBER GLOVE ORCATHETER PACKAGE describes sterile surgical elements in a strippablelaminate container using a finely divided polyglycolic acid or relatedpolymer as a lubricant for the surface of the rubber elements.

U.S. Pat. No. 3,846,382 -- Ramsey and Delapp -- Nov. 5, 1974 STERILEMEDICAL DUSTING POWDER discloses a method of dissolving polyglycolicacid in hot dimethyl sulfoxide, chilling, filtering, washing withisopropanol and with recovering finely divided polyglycolic acid.

U.S. Pat. No. 3,632,754 -- Jan. 4, 1972 -- Balassa -- USE OF CHITIN FORPROMOTING WOUND HEALING teaches the application of a powder or solutionof chitin or a chitin derivative to accelerate the rate of wound healingin a mammal.

Application Ser. No. 558,526 -- Capozza -- Mar. 14, 1975, now U.S. Pat.No. 3,988,411 SPINNING AND SHAPING POLY(N-ACETYL-D-GLUCOSAMINE) showsthe use of exotic solvents such as hexafluoroisopropyl alcohol andhexafluoroacetone sesquihydrate in the spinning, shaping and extrudingof poly(N-acetyl-D-glucosamine). Various surgical uses of thepoly(N-acetyl-D-glucosamine) are taught.

SUMMARY OF THE INVENTION

This invention includes a natural or synthetic rubber surgical glovehaving a lubricating coating of a finely divided biodegradable powderconsisting essentially of an enzymatically degradable form ofpoly(N-acetyl-D-glucosamine) selected from the group consisting of

poly[N-acetyl-6-O-(carboxymethyl)-D-glucosamine],

poly[N-acetyl-6-O-(2'-hydroxyethyl)-D-glucosamine],

poly[N-acetyl-6-O-(ethyl)-D-glucosamine], and

poly(N-acetyl-D-glucosamine) itself

The powdered glove may be sterilized by autoclaving with no adverseeffect upon the desirable properties of the powder, such as, forexample, the ability of the powder to flow freely without clumping. Thepowder can also be sterilized by other known methods such as, forexample, gaseous ethylene sterilization, or radiation. The powder isnon-toxic to living tissue and non-irritating to the skin.

The novel powder of this invention provides the medical profession witha lubricant powder which is absorbable by living tissue and which,furthermore, is non-toxic and gives no indication of causing lesions orother aggravating conditions to any substantial degree within the body.The powder is readily sterilized by autoclaving or ethylene oxide vaporand requires no elaborate pre-treatment of the powder to prevent it fromclumping during such sterilization treatments, and both before and aftersterilization the powder and the lubricated element resist hydrolyticdegredation.

Natural rubber or synthetic rubber surgical elements have many uses.Probably the most common is that of a rubber glove used by a surgeon ornurse during a surgical procedure or examination of a patient. Othersterile surgical elements may be used such as catheters, or rubberdrainage tubes which are placed in the site of a wound to permitdrainage during the healing process. Such drains are often removed assoon as the healing process proceeds to the point that a discharge is nolonger occurring. Whether the surgical elements such as a drainage tubeis to remain in the patient for a matter of several days or whether itis a surgical glove which is to be in contact with the raw tissues of awound for only a period of a few minutes, any powder on the surface ofthe rubber may be transferred into the subject. Foreign elements intissue usually cause adverse reactions. The degree of the adversereaction can vary over a wide limits but even though the reaction may beminimal, it is desired that it be reduced as far as possible.

To prevent rubber elements from sticking to each other, for example theturns of a rubber tube, or the folds of a surgical glove, it isdesirable that the surface be coated with a finely divided powder whichimparts lubricity. Lubricity is particularly necessary with a surgeonsglove in order that the glove may be easily donned.

Obviously, it is highly desirable that any such lubricating powder becompletely non-irritating to the living tissues of the subject. Althoughthe desirability of an inert powder which is completely absorbable hasbeen recognized, a powder which would meet the requirements of lubricityand still be completely absorbable with a minimal tissue reaction underany and all conditions and which is storage stable in the presence ofwater vapor has been an illusory goal.

It has now been found that the present a finely divided biodegradablepowder consisting essentially of

an enzymatically degradable form of poly(N-acetyl-D-glucosamine)selected from the group consisting of

poly[N-acetyl-6-O-(carboxymethyl)-D-glucosamine],

poly[N-acetyl-6-O-(2'-hydroxyethyl)-D-glucosamine],

poly[N-acetyl-6-O-(ethyl)-D-glucosamine], and

poly(N-acetyl-D-glucosamine) itself

imparts the desired lubricity to rubber and if present in a woundappears to be completely absorbed by living tissue within a surgicallyacceptable period of time.

Because the biggest use is that of the dusting powder for the surface ofthe surgeons glove, the present invention will be described in greatestdetail in connection with such gloves.

In the glove powder, the lubricity is the key feature and if the rubberglove having the dusting powder on its surface permits ready gloving,that is permits the surgeon to insert his hand into the glove readily,with the glove sliding onto his hand even if somewhat moist, in suchfashion as to give the feel to which the surgeon is accustomed, thepowder has filled its requirements. It is of course necessary that theglove slide on the surface of the skin of the surgeon sufficiently thatthe thin rubber membrane does not interfere with the sensitivity of thesurgeon's fingers so that the surgeon may readily feel through theglove.

DRAWINGS

In the drawings

FIG. 1 is a surgical glove having on the surface thereof

a finely divided biodegradable powder consisting essentially of

an enzymatically degradable form of poly(N-acetyl-D-glucosamine)selected from the group consisting of

poly[N-acetyl-6-O-(carboxymethyl)-D-glucosamine],

poly[N-acetyl-6-O-(2'-hydroxyethyl)-D-glucosamine],

poly[N-acetyl-6-O-(ethyl)-D-glucosamine], and

poly(N-acetyl-D-glucosamine) itself

which form of poly(N-acetyl-D-glucosamine) is slowly enzymaticallydegraded by contact with body tissues.

FIG. 2 shows a user donning a surgical glove.

FIG. 3 shows a lubricated surgical glove in a sterile package.

FIG. 4 shows a lubricated catheter in a sterile package.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The inventive dusting powder may be prepared by grinding or otherwisepulverizing

a finely divided biodegradable powder consisting essentially of

an enzymatically degradable form of poly(N-acetyl-D-glucosamine)selected from the group consisting of

poly[N-acetyl-6-O-(carboxymethyl)-D-glucosamine],

poly[N-acetyl-6-O-(2'-hydroxethyl)-D-glucosamine,

poly[N-acetyl-6-O-(ethyl)-D-glucosamine], and

poly(N-acetyl-D-glucosamine) itself

to the desired particle size by the use of conventional grindingequipment and techniques known to those skilled in the art.

The polymer may be ground in an ordinary Ball Mill. The grindingequipment is preferably grounded during the grinding operation toprevent undesirable aggregation of the particles caused by the staticelectrical charges which can accumulate on the particles duringgrinding. The ground material can then be removed from the mill andvibrated through a series of screens of varying mesh mounted on a Ro-Taptesting sieve shaker as supplied by W. S. Tyler Co.

Particle size of the ground polymer is an important criteria inselecting a powder which is suitable for a glove powder.

It is desirable that all the powder particles be small enough to passthrough a 100 mesh screen (149 micron designation in the U.S. SieveSeries). However, small amounts (up to about 1 percent by weight) ofsomewhat larger sized particles can also be present in the powderwithout undue adverse effect on the lubricating properties of thepolyglycolic acid powder. It is preferred that all of the powderparticles pass through a 200 mesh screen (74 micron designation in theU.S. Sieve Series). Passage through such a screen indicates theparticles contain not more than one dimension exceeding about 74microns.

In preparing the glove powder it is equally important that it not bemade too fine in order to minimize the escape of excessive powder intothe environment in the course of powdering the hands, surgical gloves,or other items. The powder, on the other hand, should not be of anexcessively large particle size nor should it contain substantialamounts of exceptionally large particles since this will create anundesirable abrasive effect upon the skin of the hand when the powder isused. A suitable particle size range is from about 0.5 to about 149microns with a range of from about 10 to 50 microns preferred.

Glove powder is used in a variety of ways by the medical profession.Rubber surgical gloves are typically sold unsterile in pairs with apackage of glove powder inserted in the cuff of one of the gloves. Whenit is desired to use the gloves, the gloves and the package of glovepowder are sterilized, usually by autoclaving. The surgeon will thenopen the package of glove powder (the package usually contains about 1.5grams of powder) and pour the powder onto his hands. After working thepowder over the surface of his hands, the surgeon inserts his powderedhands into the surgical gloves, the glove powder providing the lubricityrequired to facilitate this insertion. In cases where the gloves arereusable, the gloves, at the end of the operation, will be washed,dried, inspected for holes and then repowdered, usually on both theinternal and external surfaces of the glove for subsequent reuse of theglove. This powdering is ordinarily accomplished by placing the glovesand a prescribed amount of glove powder in a tumbler and tumbling for asufficient period of time to powder the inside and outside surfaces ofthe glove. The powdered gloves are then repackaged, autoclaved, andpresented to the surgeon for use. Since the outside of the glove isoften powdered it is readily apparent how some of the powder may spilloff the glove and into the exposed surgical cavity of a patient.

Disposable surgical gloves usually made of latex are also available tothe medical profession. These gloves can be offered as a unit of onepair of gloves and one package of glove powder contained in a suitablepackage. However, they are ordinarily offered as a powdered glove, i.e.,the inner and outer surfaces of the glove are pre-powdered with asuitable dusting powder. When the contents of the envelope, i.e., thegloves and the powder are sterile, the entire envelope must first beautoclaved or otherwise sterilized. At the end of the operation thegloves are discarded.

Typical glove packages are described in U.S. Pat. Nos. 3,107,786 and3,181,695.

The gloves of the present invention may be sealed in a strippableenclosure of the type shown in U.S. Pat. No. 2,949,181, there describedfor sutures, but adaptable to surgical gloves. A larger size strippablelaminate enclosure is used for gloves.

From the foregoing it becomes apparent that the glove powder of thisinvention can be offered either separately in a single package of asuitable material or in combination with a pair of surgical gloves ineither a sterile or unsterile condition. The powder itself may be eithersterile or non-sterile.

It is desirable when a sterile powdered surgical glove, sterile powder,or a sterile combination of a surgical glove and separately packagedglove powder is to be offered, to package the aforementioned sterileitems in a sterile inner enclosure which is then packaged in a sterileouter enclosure. The outer enclosure is provided with a strippable seal,which then allows for convenient serving of said sterile item to thepotential user by merely stripping away the outer enclosure to present atotally sterile enclosure, i.e., the outer surface as well as thecontents of the inner enclosure are sterile, containing the sterile itemto the user. The user can then open the package and remove the sterileitem therein without risk of contaminating the contents from contactwith the outer surface of the inner enclosure.

Chitin has been estimated to be the second most abundant polysaccharidein nature with a synthesis in the neighborhood of a billion tons a yearby marine organisms. See Chitin, N. V. Tracey, Reviews of Pure andApplied Chemistry, Royal Australian Chemical Institute, Vol. 7, No. 1,March, 1957, pages 1 to 14.

Carboxymethylchitin is disclosed in Carbohyd, Res. 7, 483-485 (1968),Ralph Trujillo.

This article mentions the hydrolysis of both chitin andcarboxymethylchitin by lysozyme.

Poly(N-acetyl-D-glucosamine) differs from cellulose in that instead of ahydroxyl group in the 2 position on cellulose, there is an acetylaminogroup.

Prudden, Migel, Hanson, Freidrich and Balassa in "The Discovery of aPotent Pure Chemical Wound-Healing Accelerator", The American Journal ofSurgery, Vol. 119, May 1970, pages 560 to 564, disclose that chitincontaining n-acetyl glucosamine is useful to accelerate wound-healing.

The enzyme lysozyme is particularly effective in the enzymaticdegradation of the present forms of poly(N-acetyl-D-glucosamine).Various forms of poly(N-acetyl-D-glucosamine) may have differentdegradation rates, and the degradation rate may vary with the location,but with minimal tissue reaction. The poly(N-acetyl-D-glucosamine) inits own right has been shown to encourage wound healing.

The lubricant powders of the present forms ofpoly(N-acetyl-D-glucosamine) are not hydrolyzed by water and, hence,need not be kept bone dry but may be stored under ambient conditions ofmoisture for prolonged periods of time. The basicpoly(N-acetyl-D-glucosamine) may be modified by treatment to introducecarboxymethyl, hydroxyethyl or O-ethyl substituents so that the polymerhas linkages from acetyl-6-O-(carboxymethyl)-D-glucosamine units,acetyl-6-O-(2'-hydroxyethyl)-D-glucosamine units, oracetyl-6-O-(ethyl)-D-glucosamine units.

Other side chains may be placed on the glucosamine ring, or itssubstituents because the side chains may vary from methyl to long chainalkyl, including branched chains, unsaturated chains, aryl or aralkyl,and which may include halogen, alkoxy, aryloxy, aralkoxy, ether, esterand amide groups, as substituents on the side chains, the relativedistribution between aqueous and solvent components in a system can bevaried as well as water solubility or oil and solvent solubility. Also,because the size and location of the side chains affects the rate ofdegradation and the acidity of the system, the rate of enzymaticdegradation can be varied.

Lubricant powders may be made by precipitating solutions of suitableforms of poly(N-acetyl-D-glucosamine) in polyfluorinated solvents suchas hexafluoroisopropyl alcohol and hexafluoroacetone sesquihydrate ormixtures of such solvents.

(N-acetyl-D-glucosamine) has the formula: ##STR1## Groups below theplane of the paper are shown by a dotted bond.

Poly(N-acetyl-D-glucosamine) has ascribed to it the formula (ringhydrogens omitted for clarity) ##STR2##

Poly(N-acetyl-D-glucosamine) is a major component of naturally occurringchitin. The naturally occurring material has not only thepoly(N-acetyl-D-glucosamine) but also inorganic salts thought to beforms of calcium carbonate and proteinaceous material, the compositionof which is not presently known. The term "chitin" is used herein torefer to the various naturally occurring forms of chitin including theprotein and inorganic carbonate components. The term "purified chitin"is used to refer to chitin after purification to remove calciumcarbonate and other inorganic salts and various proteins which may bepresent and is essentially poly(N-acetyl-D-glucosamine). Some confusionexists in the literature in that the name chitin is used as a name forpoly(N-acetyl-D-glucosamine) without specifying whether it is anaturally occurring material containing inorganic salts and proteins orwhether the term is intended to designate purifiedpoly(N-acetyl-D-glucosamine) without specifying the degree of purity orthe character of the impurities present.

The term "enzymatically degradable" refers to a form ofpoly(N-acetyl-D-glucosamine) or its derivatives which is broken downinto body fluid soluble components. The problem of retention by the bodyor disposal is minimal or non-existent.

One convenient method of sterilizing the present lubricant powder is byheat under such conditions that any microorganisms or deleteriousmaterials are rendered inactive. Another common method is to sterilizeusing a gaseous sterilizing agent such as ethylene oxide. Other methodsof sterilizing include radiation by X-rays, gamma rays, neutrons,electrons, etc., or high intensity ultrasonic vibrational energy orcombinations of these methods. The present lubricant powders may besterilized by any of these methods, although there may be appreciablebut acceptable change in physical characteristics.

EXAMPLE 1 Purification of Chitin

A commerical grade of chitin (Cal-Biochemicals) was finely ground in aball mill overnight to pass a 6 mm screen and be retained by a 1 mmscreen. 149 g. of this finely ground material was decalcified byextracting with 825 ml. of 2N HCl at 4° C for 48 hours, in a flaskstirred with a magnetic stirrer. The material was collected bycentrifugation and washed repeatedly with water until neutral. The ashcontent was 0.4-0.5%. The decalcified chitin was then stirred at roomtemperature with 1500 ml. of 90% formic acid overnight. The mixture wascentrifuged and the residue repeatedly washed with water. The washedchitin was then suspended in 2 liters or 10% NaOH solution and heated at90°-100° C. for 2.5 hours. The solution was filtered, the cake washedwith water until neutral, washed several times with absolute ethanol andether, and dried at 40° C. under reduced pressure; yield 66 g. ofpoly(N-acetyl-D-glucosamine). Infrared spectrum (KBr pellet) shows bandsat 3500 cm⁻¹ (S), 2900 (W), 1652 (S), 1619 (S), 1550 (S), 1370 (S), 1300(M), 1070 (Broad). (S is strong, M is medium, W is weak.

EXAMPLE 2 Poly(N-Acetyl-D-Glucosamine) Membranes

Membranes of poly(N-acetyl-D-glucosamine) were prepared by dissolvingpoly(N-acetyl-D-glucosamine) from Example 1 in each of hexafluoroacetonesesquihydrate (1.4% solution) and hexafluoroisopropanol (2% solution),and casting on a glass plate. The last traces of solvent were evaporatedoff in a vacuum. The films were tough, transparent, non-tacky, flexibleand were quite pliable when hydrated yet retained adequate strength toresist manipulation. The membranes showed no hydrolysis after exposureto water for 5 days.

EXAMPLE 3 Poly[N-acetyl-6-O-(carboxymethyl)-D-glucosamine]

15 g. of the poly(N-acetyl-D-glucosamine) from Example 1 was swollenwith 100 ml. of dimethylsulfoxide (DMSO). To this highly swollensuspension was added 400 ml. of 2-propanol and the mixture was stirredvigorously under nitrogen while 40 ml. 30% aqueous NaOH was added overan interval of 30 minutes at room temperature. After stirring for anadditional hour, 18 g. of chloracetic acid dissolved in 40 ml. of waterwas added dropwise over a 30 minute period. The mixture was then heatedat 55° C. for 24 hours. The mixture was decanted and to the residue wasadded 100 ml. of 70% methanol. The suspension was then neutralized with5 ml. of 90% acetic acid. The mixture was filtered, washed with 70%methanol, absolute methanol and dried at 40° C. in vacuo. Yield 24 g. ofpoly[N-acetyl-6-O-(carboxymethyl)-D-glucosamine], I. Infrared (KBrpellet) shows bands at 3500 cm⁻¹ (S), 2900 (M), 1600 Broad (S), 1400(M), 1320 (M), 1100 Broad (S). A sample was titrated and shown to have4.03 meq acid/g indicating 100% of the repeating mers were carboxylated.Films easily removed from glass were cast from water solution and shownto be transparent, flexible and tough.

EXAMPLE 4 Biodegradability ofPoly[N-Acetyl-6-O-(Carboxymethyl)-D-Glucosamine]

After 24 hours incubation at 37° C. in phosphate buffer pH 7.2containing 1500 units/ml of lysozyme,poly[N-acetyl-6-O-(carboxymethyl)-D-glucosamine] was hydrolyzed tooligomers as determined by Gel Permeation Chromatography. A controlcontaining no enzyme was not hydrolyzed under the same conditions.

EXAMPLE 5 Poly[N-Acetyl-6-O-(2'-Hydroxyethyl)-D-Glucosamine]

Into a screw cap bottle was placed 13.6 g of purifiedpoly(N-acetyl-D-glucosamine) milled so that it passed a 1 mm. sieve. Tothe bottle was added 200 ml. of cold (0°-5° C.) aqueous 43% NaOH and thecontents stirred for 2 hours under nitrogen and then held at 0°-4° C.for 10 hours. The swollen alkali derivative was then squeezed to 3 timesits original weight in a sintered glass funnel, disintegrated and frozenat -20 C. under nitrogen for 1 hour and then thawed at room temperaturefor 1 hour. The freeze-thaw cycle was repeated 3 times. To the alkaliderivative was then added 120 ml. of dimethyl sulfoxide (DMSO) and theslurry added immediately to a stirred autoclave. The autoclave waspurged several times with nitrogen and 53.2 ml. of ethylene oxide wasadded (16 equivalents/equivalent of PAG). The mixture was held at 50° C.for 18 hours. The solution was then carefully neutralized with glacialacetic acid, dialyzed and then lyophilized.

The hydroxyethyl derivative can be further purified by precipitating thepolymer from aqueous solution with acetone. A freshly precipitatedsample of poly[N-acetyl-6-O-(2'-hydroxyethyl)-D-glucosamine] readilydissolved in water, 5% aqueous sodium hydroxide, and 3% acetic acid andis precipitated from these solutions by acetone. Samples analyzed for C,H, and N showed the composition to be one in which 1.5 hydroxyethylgroups had been substituted per glucosamine residue.

EXAMPLE 6 Poly[N-Acetyl-6-O-(Ethyl)-D-Glucosamine]

The procedure of Example 5 was followed except 75 ml. of ethylchloridewas added instead of ethylene oxide and the reaction held at 50° C. for15 hours. A water soluble derivative is obtained.

To obtain an organic soluble derivative, the ethylchloride was mixedwith benzene (75% of the amount of ethylchloride). The reaction time was10 hours and the temperature was controlled as follows: 1 hour heatingup to 60° C., 1 hour heating up to 80° C., 1 hour heating up to 130° C.and 7 hours at 130° C. An organic solvent soluble product was obtained.The following solvents are useful for solubilization (5% solution) ofthis polymer at room temperature: O-xylene, benzene, toluene,methylethyl ketone, 1.4 mixture of alcohol and benzene, chloroform andalcohols.

EXAMPLE 7

The products from each of Examples.

1, 2, 3, 5, and 6 were separately placed in a 1 quart ball mill withabout 40 grams of product and five 11/4 inch balls, ten 1 inch balls,nine 1/2 inch balls, nine 3/4 inch balls and 145/8 inch balls. The millwas grounded and rotated from a Friday afternoon to a Wednesday morning,about 113 hours; the balls separated and the product screened. About 88to 90% of the ground product passed a 325 mesh screen with an averageparticle size of about 25 microns.

A pair of gloves dusted with 11/2 grams of each of the product powderswere sealed between a polyester, polyethylene laminate as abovedescribed using a strippable seal and a group of the gloves were thenplaced in an ethylene oxide chamber to allow the ethylene oxide topenetrate through the laminate seal as described in more detail in U.S.Pat. No. 2,917,878 Canarius and Kaufman.

The individual gloves before sterilization are indicated in FIG. 1, thesurface of the glove 11 has the finely divided biodegradable powder 12spread thereover.

FIG. 2 shows the surgeon donning the glove. The glove 13 is held by anurse whose hands 14 hold the glove with the cuff slightly stretchedwhile the hand of the surgeon 15 is inserted therein to.

FIG. 3 shows the surgical glove 11, having the powder 12 on itssurfaces, folded in a paper wrapper 16, inserted in an outer strippableenvelope 17.

It is convenient to powder the glove with the finely divided polymerbefore the glove is sterilized, and sterilize the powdered glove andkeep it in sterile condition until ready for use. It is also convenientto use the powder in sterile form to be applied to the surface ofsterile gloves at the time they are being put on. The time of powderingthe glove and the time for storing can vary with the technique andschedules of the particular user, such as a hospital or individualsurgeon. If sterile gloves are used, a single use disposable glove isconvenient. If the gloves are to be reused, the time of applying thepowder and the sterilizing can be varied depending upon the number ofgloves used in the inventory available or preferences.

When used in patients during surgical procedures, no deleterious effectswhich could be ascribed to the glove powder were observed.

FIG. 4 shows a catheter 18 similarly packaged in a similar strippablepackage.

Other sizes and types of ball mills, grinding cycles or systems ofattriting may be used with good results. Natural chitin if ball milledto the preferred particle size acts as a satisfactory lubricant -- butwith various marine and fungal sources, the impurities, particularly theproteins, may vary and have different interactions with tissue.Preferably the chitin is purified and optionally chemically modified andthe resultant enzymatically degradable forms ofpoly(N-acetyl-D-glucosamine) used because of greater freedom from thepossibility of tissue reaction.

I claim:
 1. A method of minimizing tissue reaction in a surgicalprocedure which comprises contacting living tissue with a natural orsynthetic rubber surgical element having on the surface thereof alubricity imparting quantity ofa finely divided biodegradable powderconsisting essentially of an enzymatically degradable form ofpoly(N-acetyl-D-glucosamine) selected from the group consistingofpoly[N-acetyl-6-O-(carboxymethyl)-D-glucosamine],poly[N-acetyl-6-O-(2'-hydroxyethyl)-D-glucosamine,poly[N-acetyl-6-O-(ethyl)-D-glucosamine], andpoly(N-acetyl-D-glucosamine) itselfwhich form ofpoly(N-acetyl-D-glucosamine) is slowly enzymatically degraded by contactwith body tissues.
 2. The method of claim 1 in which substantially allpolymer powder particles are smaller than 200 mesh.
 3. The method ofclaim 2 in which the element and powder are sterile, and the powder ispoly[N-acetyl-6-O-(carboxymethyl)-D-glucosamine] which will pass througha 200 mesh screen.
 4. The method of claim 2 in which the element andpowder are sterile, and the powder ispoly[N-acetyl-6-O-(2'hydroxyethyl)-D-glucosamine which will pass througha 200 mesh screen.
 5. The method of claim 2 in which the element andpowder are sterile, and the powder ispoly[N-acetyl-6-O-(ethyl)-D-glucosamine] which will pass through a 200mesh screen.
 6. The method of claim 2 in which the element and powderare sterile, and the powder is poly(N-acetyl-D-glucosamine) which willpass through a 200 mesh screen.